<p>Protein tyrosine phosphatase 1B (PTP1B) and α<b>-</b>glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of <i>Paulownia tomentosa</i> fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (<b>1–8</b>) displaying dual inhibition of PTP1B and α<b>-</b>glucosidase. The isolated compounds were identified as flavanones (<b>1–5</b>) and dihydroflavonols (<b>6–8</b>). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC<sub>50</sub> = 1.9–8.2 μM) than α<b>-</b>glucosidase (IC<sub>50</sub> = 2.2–78.9 μM). Mimulone (<b>1</b>) was the most effective against PTP1B with IC<sub>50</sub> = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (<b>8</b>) displayed potent inhibition against α<b>-</b>glucosidase (IC<sub>50</sub> = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in <i>V</i><sub>max</sub>, an increase of <i>K</i><sub>m</sub>, and <i>K</i><sub>ik</sub>/<i>K</i><sub>iv</sub> ratio ranging between 2.66 and 3.69.</p>